Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrestCentral MessagePerspective
Objectives: Acute kidney injury is a serious complication after cardiovascular surgery requiring circulatory arrest. It is reported that mice can be induced into a hibernation-like hypometabolic state by stimulating a specific neuron located at the hypothalamus (quiescence-inducing neurons-induced h...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-12-01
|
| Series: | JTCVS Open |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666273622003734 |
| _version_ | 1797991335838351360 |
|---|---|
| author | Shoichi Kyo, MD Kozue Murata, PhD Masahide Kawatou, MD, PhD Kenji Minatoya, MD, PhD Genshiro A. Sunagawa, MD, PhD Hidetoshi Masumoto, MD, PhD |
| author_facet | Shoichi Kyo, MD Kozue Murata, PhD Masahide Kawatou, MD, PhD Kenji Minatoya, MD, PhD Genshiro A. Sunagawa, MD, PhD Hidetoshi Masumoto, MD, PhD |
| author_sort | Shoichi Kyo, MD |
| collection | DOAJ |
| description | Objectives: Acute kidney injury is a serious complication after cardiovascular surgery requiring circulatory arrest. It is reported that mice can be induced into a hibernation-like hypometabolic state by stimulating a specific neuron located at the hypothalamus (quiescence-inducing neurons-induced hypometabolism [QIH]). Here, we investigated the efficacy of QIH for the amelioration of acute kidney injury in an experimental circulatory arrest using a transgenic mouse model. Methods: We genetically prepared mice in which QIH can be conditionally induced (QIH-ready mice). Mice were divided into 4 groups (n = 6 for each): QIH-ready normothermia (QN), QIH-ready hypothermia (QH), control normothermia (CN), and control hypothermia (CH). After induction of QIH, left thoracotomy and descending aorta crossclamping were conducted. After reperfusion, we collected kidneys and evaluated histologic changes and serum biochemical markers, specifically neutrophil gelatinase-associated lipocalin and cystatin C, indicating early kidney injury. Results: Normothermia showed higher tubular injury scores than those in hypothermia (QN vs QH [P = .0021] and CN vs CH [P < .001]). QN exhibited lower neutrophil gelatinase-associated lipocalin and cystatin C levels than those in CN (neutrophil gelatinase-associated lipocalin: CN vs QN: 1.51 ± 0.71 vs 0.82 ± 0.32; P = .0414 and cystatin C: 1.48 ± 0.39 vs 0.71 ± 0.26; P = .0015). There was no significant difference between QN and QH. Conclusions: QIH partly ameliorated acute kidney injury in a mouse ischemia model even in normothermia. QIH might be a promising approach to achieving sufficient kidney protection without hypothermic circulatory arrest in the future. |
| first_indexed | 2024-04-11T08:49:29Z |
| format | Article |
| id | doaj.art-42237b89ea2f4aa6a1c46d00722e0a39 |
| institution | Directory Open Access Journal |
| issn | 2666-2736 |
| language | English |
| last_indexed | 2024-04-11T08:49:29Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTCVS Open |
| spelling | doaj.art-42237b89ea2f4aa6a1c46d00722e0a392022-12-22T04:33:36ZengElsevierJTCVS Open2666-27362022-12-0112201210Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrestCentral MessagePerspectiveShoichi Kyo, MD0Kozue Murata, PhD1Masahide Kawatou, MD, PhD2Kenji Minatoya, MD, PhD3Genshiro A. Sunagawa, MD, PhD4Hidetoshi Masumoto, MD, PhD5Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Clinical Translational Research Program, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan; Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, JapanDepartment of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanLaboratory for Molecular Biology of Aging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan; Laboratory for Hibernation Biology, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanDepartment of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Clinical Translational Research Program, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan; Address for reprints: Hidetoshi Masumoto, MD, PhD, Clinical Translational Research Program, RIKEN Center for Biosystems Dynamics Research, 2 -2 -3 Minatojima-minimachi, Chuo-ku, Kobe 650–0047, Japan.Objectives: Acute kidney injury is a serious complication after cardiovascular surgery requiring circulatory arrest. It is reported that mice can be induced into a hibernation-like hypometabolic state by stimulating a specific neuron located at the hypothalamus (quiescence-inducing neurons-induced hypometabolism [QIH]). Here, we investigated the efficacy of QIH for the amelioration of acute kidney injury in an experimental circulatory arrest using a transgenic mouse model. Methods: We genetically prepared mice in which QIH can be conditionally induced (QIH-ready mice). Mice were divided into 4 groups (n = 6 for each): QIH-ready normothermia (QN), QIH-ready hypothermia (QH), control normothermia (CN), and control hypothermia (CH). After induction of QIH, left thoracotomy and descending aorta crossclamping were conducted. After reperfusion, we collected kidneys and evaluated histologic changes and serum biochemical markers, specifically neutrophil gelatinase-associated lipocalin and cystatin C, indicating early kidney injury. Results: Normothermia showed higher tubular injury scores than those in hypothermia (QN vs QH [P = .0021] and CN vs CH [P < .001]). QN exhibited lower neutrophil gelatinase-associated lipocalin and cystatin C levels than those in CN (neutrophil gelatinase-associated lipocalin: CN vs QN: 1.51 ± 0.71 vs 0.82 ± 0.32; P = .0414 and cystatin C: 1.48 ± 0.39 vs 0.71 ± 0.26; P = .0015). There was no significant difference between QN and QH. Conclusions: QIH partly ameliorated acute kidney injury in a mouse ischemia model even in normothermia. QIH might be a promising approach to achieving sufficient kidney protection without hypothermic circulatory arrest in the future.http://www.sciencedirect.com/science/article/pii/S2666273622003734circulatory arrestacute kidney injuryhibernationQ neurons-induced hypometabolism |
| spellingShingle | Shoichi Kyo, MD Kozue Murata, PhD Masahide Kawatou, MD, PhD Kenji Minatoya, MD, PhD Genshiro A. Sunagawa, MD, PhD Hidetoshi Masumoto, MD, PhD Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrestCentral MessagePerspective JTCVS Open circulatory arrest acute kidney injury hibernation Q neurons-induced hypometabolism |
| title | Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrestCentral MessagePerspective |
| title_full | Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrestCentral MessagePerspective |
| title_fullStr | Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrestCentral MessagePerspective |
| title_full_unstemmed | Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrestCentral MessagePerspective |
| title_short | Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrestCentral MessagePerspective |
| title_sort | quiescence inducing neurons induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrestcentral messageperspective |
| topic | circulatory arrest acute kidney injury hibernation Q neurons-induced hypometabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2666273622003734 |
| work_keys_str_mv | AT shoichikyomd quiescenceinducingneuronsinducedhypometabolismamelioratesacutekidneyinjuryinamousemodelmimickingcardiovascularsurgeryrequiringcirculatoryarrestcentralmessageperspective AT kozuemurataphd quiescenceinducingneuronsinducedhypometabolismamelioratesacutekidneyinjuryinamousemodelmimickingcardiovascularsurgeryrequiringcirculatoryarrestcentralmessageperspective AT masahidekawatoumdphd quiescenceinducingneuronsinducedhypometabolismamelioratesacutekidneyinjuryinamousemodelmimickingcardiovascularsurgeryrequiringcirculatoryarrestcentralmessageperspective AT kenjiminatoyamdphd quiescenceinducingneuronsinducedhypometabolismamelioratesacutekidneyinjuryinamousemodelmimickingcardiovascularsurgeryrequiringcirculatoryarrestcentralmessageperspective AT genshiroasunagawamdphd quiescenceinducingneuronsinducedhypometabolismamelioratesacutekidneyinjuryinamousemodelmimickingcardiovascularsurgeryrequiringcirculatoryarrestcentralmessageperspective AT hidetoshimasumotomdphd quiescenceinducingneuronsinducedhypometabolismamelioratesacutekidneyinjuryinamousemodelmimickingcardiovascularsurgeryrequiringcirculatoryarrestcentralmessageperspective |